ALFERROCK

Endpoint summary

Description of key information

According to the results of specific bioelution testing with the test substance (Klawonn, 2021, please see IUCLID section 7.1.1), aluminium has the highest relative release into artificial physiological media representing relevant exposure routes and therefore was considered as main constituent for the human health hazard/risk assessment of Alferrock. Release of aluminium into Artificial sweat solution (pH = 6.5) simulates an exposure scenario in contact with human skin. Under condition of the bioelution test, aluminium ions show very low release in the Artificial sweat solution. (33.2 µg /1 g of Alferrock and150.3 µg /1 g of Alferrock after 2 and 24 hours respectively, see IUCLID section 7.1.1).

Contact sensitivity to aluminium is very rare. Several review articles report a low incidence of hypersensitization of aluminium compounds even after subcutaneous and intramuscular injections. The risk of hypersensitization after dermal application of a poorly soluble compound like aluminium from Alferrock is considered to be lower compared to subcutaneous injection. Therefore, conducting a test with Alferrock is considered to be scientifically unjustified.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

For human health endpoints, the relative bioavailability of different metal-ions from ALFERROCK would determine its potential to cause toxicological effects and also govern the severity of such effects. Aluminium ions show very low release in the Artificial sweat solution (33.2 µg/g of Alferrock within 2h and 150.3 µg/g of Alferrock after 24 hours (Klawonn, 2021, please see IUCLID section 7.1.1)). According to an in vivo skin penetration study conducted by Flarend et al. (2001) [A preliminary study of the dermal absorption of aluminium from antisperspirants using aluminium-26, Food Chem Toxicol 2001, 39(2): 163-168] the dermal absorption of aluminium (from aluminium chlorohydrate) was estimated at 0.012 %. Therefore, exposure to aluminium from Alferrock by the dermal route is considered negligible. It can be assumed, that the dermal exposure is at the same order of magnitude or lower compared to other poorly soluble aluminium compounds, which are used in antiperspirants and known to very rarely elicit allergic contact dermatitis. In addition, Nordberg et al. (2015) [Handbook on the Toxicology of Metals, Fourth Edition, Academic Press] concluded that allergic contact dermatitis from aluminium is rare. The risk of sensitisation is higher from injection of aluminium-adsorbed vaccines. Itching nodules were found in 645 children out of 76,000 vaccines (0.8%) after subcutaneous and intramuscular injections. A majority of the affected children (75%) had symptoms after a median duration of 4 years, and 77% of the children with nodules showed contact hypersensitivity to aluminium. Sensitisation has also occurred after aluminium particles were accidentally impelled into the skin from a compressed air pistol. Tattooing with aluminium silicate to create blepharopigmentation has resulted in a delayed hypersensitivity granulomatous reaction. The same conclusion was drawn in a review article from Krewski et al. (2007) [Human health risk assessment for Aluminium, Aluminium oxide, and Aluminium hydroxide, J Toxicol Environ Health B Crit Rev., 2007 ; 10 (Suppl 1): 1–269], and the subsequent update thereof by Willhite et al. (2014) [Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts, Crit Rev Toxicol, 2014; 44(S4): 1–80] Krewski (2007) and Willhite (2014) concluded that contact sensitivity to aluminium is very rare. Sensitisation has occurred after injection of aluminium-adjuvant containing vaccines and pollen extracts, resulting in persistent granuloma at the injection site. These effects are much more frequent with aluminium hydroxide than aluminium phosphate adjuvants and more commonly seen following subcutaneous (s.c.) than i.m. injection. Less common is sensitivity during continuous application of aluminium containing antiperspirants, topical aluminium application, and occupational exposure to aluminium dust and filings which result in recurrent eczema. Based on the low incidence of hypersensitization after subcutaneous and intramuscular injections, the risk of hypersensitization after dermal application of a poorly soluble compound like aluminium from Alferrock is considered negligible. Conducting a test with target substance is therefore considered to be scientifically unjustified.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to the results of the bioelution testing (see IUCLID section 7.1.1), aluminium has the highest relative release into artificial physiological media and therefore was considered as main constituent for the human health hazard/risk assessment of Alferrock. For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Contact sensitivity to aluminium is very rare. Several review articles report a low incidence of hypersensitization of aluminium compounds even after subcutaneous and intramuscular injections. The risk of hypersensitization after dermal application of a poorly soluble compound like aluminium fromAlferrockis considered to be lower compared to subcutaneous injection. Therefore, classification for Skin Sensitisation according to the criteria of Annex I of Regulation (EC) 1272/2008 (CLP Regulation) is not warranted.